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Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production.

Publication ,  Journal Article
Chen, Y-C; Shen, S-C; Lee, W-R; Hsu, F-L; Lin, H-Y; Ko, C-H; Tseng, S-W
Published in: Biochem Pharmacol
December 15, 2002

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, including emodin, physcion, and chrysophanol, emodin showed the most potent cytotoxic effects on HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, appearance of apoptotic bodies, and an increase in hypodiploid cells. Emodin at apoptosis-inducing concentrations causes rapid and transient induction of caspase 3/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP-ribose) polymerase and D4-GDI proteins, the appearance of cleaved caspase 3 fragments being detected in emodin- but not physcion- or chrysophanol-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in emodin-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bad remained unchanged. The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD-CHO, attenuated emodin-induced DNA ladders, associated with the blockage of PARP and D4-GDI cleavage. Free radical scavenging agents including NAC, catalase, SOD, ALL, DPI, L-NAME and PDTC showed no preventive effect on emodin-induced apoptotic responses, whereas NAC, CAT and PDTC prevented HL-60 cells from ROS (H(2)O(2))-induced apoptosis through inhibition of caspase 3 cascades. Induction of catalase, but not SOD, activity was detected in emodin-treated HL-60 cells by in gel activity assays, and H(2)O(2)-induced intracellular peroxide level was significantly reduced by prior treatment of emodin in HL-60 cells. Our experiments provide evidence that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.

Duke Scholars

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

December 15, 2002

Volume

64

Issue

12

Start / End Page

1713 / 1724

Location

England

Related Subject Headings

  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • rho Guanine Nucleotide Dissociation Inhibitor beta
  • Superoxide Dismutase
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-bcl-2
  • Proteins
  • Poly(ADP-ribose) Polymerases
  • Poly (ADP-Ribose) Polymerase-1
  • Pharmacology & Pharmacy
  • Oligopeptides
 

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Chen, Y.-C., Shen, S.-C., Lee, W.-R., Hsu, F.-L., Lin, H.-Y., Ko, C.-H., & Tseng, S.-W. (2002). Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol, 64(12), 1713–1724. https://doi.org/10.1016/s0006-2952(02)01386-2
Chen, Yen-Chou, Shing-Chuan Shen, Woan-Ruoh Lee, Foun-Lin Hsu, Hui-Yi Lin, Ching-Huai Ko, and Shi-Wen Tseng. “Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production.Biochem Pharmacol 64, no. 12 (December 15, 2002): 1713–24. https://doi.org/10.1016/s0006-2952(02)01386-2.
Chen Y-C, Shen S-C, Lee W-R, Hsu F-L, Lin H-Y, Ko C-H, et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol. 2002 Dec 15;64(12):1713–24.
Chen, Yen-Chou, et al. “Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production.Biochem Pharmacol, vol. 64, no. 12, Dec. 2002, pp. 1713–24. Pubmed, doi:10.1016/s0006-2952(02)01386-2.
Chen Y-C, Shen S-C, Lee W-R, Hsu F-L, Lin H-Y, Ko C-H, Tseng S-W. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem Pharmacol. 2002 Dec 15;64(12):1713–1724.
Journal cover image

Published In

Biochem Pharmacol

DOI

ISSN

0006-2952

Publication Date

December 15, 2002

Volume

64

Issue

12

Start / End Page

1713 / 1724

Location

England

Related Subject Headings

  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • rho Guanine Nucleotide Dissociation Inhibitor beta
  • Superoxide Dismutase
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-bcl-2
  • Proteins
  • Poly(ADP-ribose) Polymerases
  • Poly (ADP-Ribose) Polymerase-1
  • Pharmacology & Pharmacy
  • Oligopeptides